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Research Project

ROLE OF A SHORT CHAIN DEHYDROGENASE/REDUCTASE IN TISSUE MINERALIZATION

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Dietary lipid quality regulates bone composition and metabolism in gilthead seabream (Sparus aurata) juveniles
Publication . Dias, J.; Rodrigues, V.; Colen, Rita; Rosa, Joana; Viegas, Michael; Cardeira Da Silva, João; Cancela, Leonor; Gavaia, Paulo J.; Laizé, Vincent
Replacement of significant amounts of marine fish oils by vegetable oils is a major trend in the aquaculture feed industry. However, knowledge on the mechanisms underlying the nutritional regulation of bone metabolism is extremely scarce in fish. We speculate that changes in the dietary ratio of fatty acids may modulate tissue eicosanoids production and affect bone formation in fastgrowing gilthead seabream, an important fish species for aquaculture in the Mediterranean region.
Central role of betaine-homocysteine S-methyltransferase 3 in chondral ossification and evidence for sub-functionalization in neoteleost fish
Publication . Rosa, Joana; Tiago, Daniel; Marques, Cátia L.; Vijayakumar, Parameswaran; Fonseca, Luís; Cancela, Leonor; Laizé, Vincent
Background: To better understand the complex mechanisms of bone formation it is fundamental that genes central to signaling/regulatory pathways and matrix formation are identified. Cell systems were used to analyze genes differentially expressed during extracellular matrix mineralization and bhmt3, coding for a betaine-homocysteine S-methyltransferase, was shown to be down-regulated in mineralizing gilthead seabream cells.Methods: Levels and sites of bhmt3 expression were determined by qPCR and in situ hybridization throughout seabream development and in adult tissues. Transcriptional regulation of bhmt3 was assessed from the activity of promoter constructs controlling luciferase gene expression. Molecular phylogeny of vertebrate BHMT was determined from maximum likelihood analysis of available sequences.Results: bhmt3 transcript is abundant in calcified tissues and localized in cartilaginous structures undergoing endo/perichondral ossification. Promoter activity is regulated by transcription factors involved in bone and cartilage development, further demonstrating the central role of Bhmt3 in chondrogenesis and/or osteogenesis. Molecular phylogeny revealed the explosive diversity of bhmt genes in neoteleost fish, while tissue distribution of bhmt genes in seabream suggested that neoteleostean Bhmt may have undergone several steps of sub-functionalization.Conclusions: Data on bhmt3 gene expression and promoter activity evidences a novel function for betaine-homocysteine S-methyltransferase in bone and cartilage development, while phylogenetic analysis provides new insights into the evolution of vertebrate BHMTs and suggests that multiple gene duplication events occurred in neoteleost fish lineage.General significance: High and specific expression of Bhmt3 in gilthead seabream calcified tissues suggests that bone-specific betaine-homocysteine S-methyltransferases could represent a suitable marker of chondral ossification.

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Fundação para a Ciência e a Tecnologia

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Funding Award Number

SFRH/BD/47433/2008

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